Upon doxycycline withdrawal at 8 weeks of age, mice developed progressive cerebellar ataxia by 26 weeks and succumbed by 30 weeks...Prophylactic administration of the CSF1R inhibitor BLZ945 exacerbated motor deficits and demyelination, significantly increasing this microglial population. Similarly, MSR1+ and CD68+ microglia/macrophages were observed in early pontocerebellar lesions of six human MSA-C autopsy cases. These findings suggest that this pro-inflammatory microglia subset plays a central role in disease progression and may represent a promising therapeutic target for modifying the course of MSA-C and related synucleinopathies.

P=N/A, N=80, Not yet recruiting, Blueprint Medicines Corporation

P1/2, N=155, Active, not recruiting, Fujian Haixi Pharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting

Functional validation was conducted using a ccRCC xenograft mouse model treated with the CSF1R inhibitor Sotuletinib...Importantly, CellChat-based predictions represent potential, rather than definitive, ligand-receptor interactions, and thus require further mechanistic validation. Targeting CSF1R may offer a promising strategy to modulate the immune landscape and improve therapeutic outcomes in ccRCC.

Microglia inhibition or depletion by treating organotypic cultures with minocycline or PLX3397 resulted in reduced levels of all the evaluated cytokines in the medium, confirming the role of microglia in the inflammatory microenvironment of glioblastoma. These findings provide valuable insights into how microglia interact with tumors and healthy cells in the tumor microenvironment, driving neuroinflammation and tumor cell dedifferentiation. This understanding could pave the way for the development of innovative therapies for glioblastoma.

P1, N=20, Completed, Abbisko Therapeutics Co, Ltd | Active, not recruiting --> Completed

Increasing evidence suggests that a subset of CCA patients can benefit from multiple tyrosine kinase inhibitors (mTKIs) such as surufatinib...Furthermore, cancer-associated fibroblasts (CAFs) were identified as the major source of IGF1 in CCA microenvironment, essential for IGF1R-driven tumor progression.In summary, the PTPN9-IGF1R axis plays a pivotal role in modulating mTKI sensitivity and tumor progression in CCA. This axis serves as a promising biomarker for identifying potential mTKI beneficiaries and represents a potential therapeutic target to enhance mTKI efficacy and overcome resistance.

This system, MRC1-targeting peptide-M@BLZ945 (PMMB), integrates a colony-stimulating factor 1 receptor (CSF-1R) inhibitor and a STING agonist within a macrophage-mimetic nanostructure, enabling sequential, controlled reprogramming of TAMs...These findings establish spatiotemporal macrophage circuit engineering via STING phase separation as a cross-scale strategy to override PDAC's immune barriers and drive next-generation macrophage-targeted immunotherapy. This study paves the way for rationally designed, precision macrophage modulation strategies in solid tumors.

P1/2, N=37, Active, not recruiting, Blueprint Medicines Corporation | Trial primary completion date: Feb 2025 --> Nov 2025

P1, N=24, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1/2 --> P1 | Not yet recruiting --> Recruiting

From August 2019 to October 2020, he received long-acting octreotide and transarterial chemoembolization (TACE), achieving stable disease...In September 2022, oral surufatinib was initiated but paused in September 2023 due to adverse effects...This case demonstrates that everolimus can induce SSTR re-expression in advanced, SSTR-negative pNETs, offering new therapeutic possibilities. The "induction plus re-evaluation" approach could guide personalized treatment strategies in late-stage pNETs, although further studies are needed to validate this approach.

P1, N=20, Recruiting, Deciphera Pharmaceuticals, LLC | Not yet recruiting --> Recruiting